Because of the importance of three-dimensional (3D) structure (microenvironment) to the cell function, a goal in metabolic and tissue engineering is to control the spatial arrangement of cells to mimic the 3D ordering of cells in native tissues. To date, many efforts toward this goal have focused on two-dimensional (2D) patterns using photolithography or microcontact printing of a single cell type. The 2D cell patterns provide two types of micrometer-scale regions, one in which the cells adhere, while the other has low cell adhesion. The design intent is for the cells to adhere selectively to the patterned regions of high adhesion.
The aforementioned lithographic process is somewhat successful for one cell type; however, culturing more than one cell type requires differential adhesion between the two cell types. The lithographic process falls short of the true 3D mark required to create the proper microenvironment for cell growth.
Current approaches, to include transplantation, transfusion of cells into a preformed implantable biocompatible matrix, or 2D in vitro culturing of tissues, require both expensive and timely custom fabrication and tremendously invasive surgeries.
A recent review article by Jung et al. articulates the importance of topographical and physiochemical modification—the microenvironment—of the material surface to enable patterning of living cells. See D. R. Jung, R. Kapur, T. Adams, K. A. Giuliano, M. Mrksich, H. G. Craighead, and D. L. Taylor, Critical Reviews in Biotechnology 2001, 21, 111, which is expressly incorporated herein in its entirety by this reference. The article provides several examples of the precise control of the architecture of multiple cells via precise engineering of the material surface (cell patterning). It is shown that selective phenotypic and genotypic control of living tissues is provided by surface topographic and physiochemical treatments. Surface is italicized above to illustrate that while this technology is highly successful for such applications as cell-based assays for drug discovery and planar biosensor arrays, it does not satisfy the 3D requirements for metabolic and tissue engineering.
Existing tissue and organ losses are treated by transplantation of an organ from a donor, through surgical reconstruction, or by the use of a mechanical-type substitute. Most potential recipients die waiting for available transplant organs. Those fortunate enough to receive a donor organ are relegated to a lifetime of immunosuppression therapy. The option of surgical reconstruction, although usually involving the patient's own tissues, again is not appropriate for many situations and is associated with significant morbidity. The burden to the patient and the health-care delivery system due to the extensive surgery often required and the high number of repeat procedures is no longer inline with the objectives of modern treatment preferences. Mechanical devices, such as kidney dialysis machines, provide a therapeutic value but represent a mere life-sustaining function for now and in the future.
Thus, a need exists to recreate the 3D relations among cells and bioactive substances that are necessary to normal tissue morphogenesis and organ functions through a tool that introduces the new constructs with minimal trauma to the host. A need exists for a tool that combines additive and subtractive processes in one integrated embodiment. For biological and/or medical applications, this is especially true if the tool can be integrated with minimally invasive surgery (MIS) techniques. A need also exists for technologies that enable such a tool and its use, including pumping systems, material delivery and mixing systems, position control systems, material dispensing systems, material destruction and removal systems, material temperature control systems, imaging and detection systems, and therapeutic systems.